Orexins A and B (or hypocretins 1 and 2) are hypothalamic neuropeptides of 33 and 28 amino acids respectively, that were recently identified as endogenous ligands of two receptors having seven transmembrane domains, named orexin 1 and orexin 2 receptors (Sakurai T., Cell, Vol. 92, 573-585, 1998; De Lecea L., Proc. Natl. Acad. Sci., Vol. 95, 322-327, 1998).
The orexin 2 receptor has the property of recognizing the two forms of orexin A and B in an equivalent manner. On the other hand, the orexin 1 receptor, which exhibits 64% homology with the orexin 2 receptor, is more selective and binds orexin A ten times better than orexin B (Sakurai T., Cell, Vol. 92, 573-585, 1998).
Via these receptors, orexins control various central and peripheral functions, in particular food and drink intake, certain cardiovascular endocrine functions and the wake/sleep cycle (Sakurai T., Regulatory Peptides, Vol. 85, 25-30, 1999).
It has now been found that some sulfonamide derivatives have a high affinity for the orexin 2 receptors and are potent antagonists of these receptors.